Fluorescent agent concentration measuring apparatus, dose control apparatus, administration system, fluorescent agent concentration measuring method, and dose control method

ABSTRACT

A fluorescent agent accumulation concentration measuring apparatus is configured to include a single-wavelength LED to radiate excitation light to a test bottle loaded in the inside, a barrier filter to transmit only fluorescence from the test bottle, a photoreceptor to receive the fluorescence through the barrier filter and output an electric signal, a detection processing circuit to conduct signal processing of the electric signal from the photoreceptor and detect the fluorescence intensity, and an operation circuit  26  to compare the detection result from the detection processing circuit with an analytical pattern stored in a pattern storage portion and calculate the peak time of the accumulation concentration in a tissue of a sample in the test bottle.

This application claims benefit of Japanese Applications No. 2005-004577filed in Japan on Jan. 11, 2005 and, No. 2005-291599 filed in Japan onOct. 4, 2005 and No. 2005-370668 filed in Japan on Dec. 22, 2005, thecontents of which are incorporated by this reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a fluorescent agent concentrationmeasuring apparatus and a fluorescent agent concentration measuringmethod, wherein the concentration of a fluorescent agent in a livingbody is measured, and furthermore, to a dose control apparatus, anadministration system, and a dose control method, wherein a fluorescencestate of an inspection object is maintained favorably when a fluorescentdrug is administered by using the fluorescent agent concentrationmeasuring apparatus and fluorescence observation is conducted with afluorescence endoscope or the like.

2. Related Art Statement

In recent yeas, a technology in which autofluorescence from a livingbody or fluorescence from a drug injected into a living body is detectedas a two-dimensional image, and degeneration of a living body tissue anda status of disease, e.g., a cancer, (for example, type of disease andrange of humectation) are diagnosed from the fluorescence figure thereofis disclosed in U.S. Pat. No. 4,556,057 and U.S. Pat. No. 5,042,494.

When light is radiated to a living body tissue, fluorescence with awavelength longer than that of the excitation light is emitted. Examplesof phosphors in the living body include NADH (nicotinamide adeninenucleotide), FMN (flavin mononucleotide), and pyridine nucleotide.Recently, the correlations between these living-body internal causesubstances and diseases are becoming clear.

Furthermore, fluorescent agents, e.g., HpD (hematoporphyrin), Photofrin,and ALA (δ-amino levulinic acid), serving as drugs to emit fluorescencehave a property of accumulating on a cancer and, therefore, diseasesites can be diagnosed by injecting these fluorescent agents into livingbodies and conducting fluorescence observation.

Technologies for endoscopically diagnosing a lesion site based on theabove-described fluorescence include fluorescence observation endoscopeapparatuses disclosed in, for example, Japanese Unexamined PatentApplication Publication No. 8-224208 and the like.

In recent years, a diagnosis and treatment method in which a fluorescentdrug having an affinity for lesions, e.g., a cancer, is administeredbeforehand in the body of an inspection object, excitation light toexcite the drug is radiated and, thereby, fluorescence from the drugaccumulated on the lesion is detected has been noted.

For example, Japanese Unexamined Patent Application Publication No.10-201707 discloses an endoscope apparatus in which the light emittedfrom a lamp is adjusted to have a wavelength band including infraredexcitation light and visible light by a band-pass filter, and isradiated through a light guide fiber of the endoscope to an inspectionobject administered with a indocyanine green derived labeled antibodywhich is excited in an infrared region and emits fluorescence, so thatthe diagnosis and treatment can be conducted while a fluorescence figureand a normal image by the visible light are displayed on a monitor.

Furthermore, PCT Japanese Translation Patent Publication No. 2000-507129discloses an intraveneous injection control apparatus in which acalibrated coding device, e.g., a calibrated rotatable knob, capable ofsetting variably a desired value and a microcontroller provided with aprogram of pharmacological model are included and the concentration of adrug fluid in the blood or the like is kept constant based on thepharmacological model during execution of injection by the user.

SUMMARY OF THE INVENTION

A fluorescent agent concentration measuring apparatus according to thepresent invention has a feature that the peak timing of accumulationconcentration of a fluorescent agent on a living body tissue iscalculated appropriately. A dose control apparatus according to thepresent invention has a feature that a favorably stable fluorescenceobservation under fluorescence intensity close to its peak is madepossible, and an improvement in diagnostic performance and a reductionof observation time can be achieved.

The fluorescent agent concentration measuring apparatus of the presentinvention includes an excitation light source to radiate excitationlight to a sample containing a body fluid taken from a living bodyadministered with a fluorescent drug, the excitation light allowing thedrug to emit fluorescence; a fluorescence detection portion to detectthe fluorescence; a fluorescent agent concentration calculation portionto calculate the concentration of the drug in the living body, based ona detection signal from the fluorescence detection portion; and a peaktime estimation portion to estimate the peak time of the concentrationof the drug in the living body tissue, based on the elapsed time afteradministration of the drug to the living body and the calculatedconcentration of the drug.

The dose control apparatus of the present invention includes thefluorescent agent concentration measuring apparatus; an administrationstart judgment portion to judge whether a predetermined time has elapsedor not and to judge the start of administration of the drug when thepredetermined time has elapsed; a dose setting portion to set at leastone of the dose and the administration time of the drug, based on thepredetermined dose information of the drug after the judgment of thestart of administration by the administration start judgment portion; anoutput apparatus to perform at least one of functions of allowing amonitor portion for monitoring to display the dose and allowing anautomatic administration apparatus to administer the drug, based on thedose of the drug set by the dose setting portion; and a living bodyinformation detection portion to detect living body function informationof the living body and to transmit the living body function informationto the dose setting portion.

Other features and advantages will be made clear by the followingdescription.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an external view showing the appearance of a fluorescent agentconcentration measuring apparatus according to a first embodiment of thepresent invention.

FIG. 2 is a diagram showing a first display example of a display portionshown in FIG. 1.

FIG. 3 is a block diagram showing the configuration of the fluorescentagent concentration measuring apparatus shown in FIG. 1.

FIG. 4 is a diagram showing light absorption and light emissioncharacteristics of a sample in a test bottle shown in FIG. 2.

FIG. 5 is a diagram showing a transmission characteristic of a barrierfilter shown in FIG. 2.

FIG. 6 is a block diagram showing the configuration of a modification ofthe fluorescent agent concentration measuring apparatus shown in FIG. 1.

FIG. 7 is a diagram showing a transmission characteristic of anexcitation light filter shown in FIG. 6.

FIG. 8 is a flow chart for explaining operations of the fluorescentagent concentration measuring apparatus shown in FIG. 2.

FIG. 9 is a diagram showing an example of an analytical pattern groupstored in a pattern storage portion shown in FIG. 2 and composed of aplurality of analytical patterns reflecting the individual difference ona fluorescent agent basis.

FIG. 10 is a diagram for explaining processing for comparing with eachanalytical pattern of the analytical pattern group, shown in FIG. 8.

FIG. 11 is a diagram showing a second display example of the displayportion shown in FIG. 1.

FIG. 12 is a block diagram showing the configuration of a fluorescentagent concentration measuring apparatus according to a second embodimentof the present invention.

FIG. 13 is an explanatory diagram of an entire system when afluorescence observation is conducted with an endoscope by using a dosecontrol apparatus according to a third embodiment of the presentinvention.

FIG. 14 is a functional block diagram of the dose control apparatusshown in FIG. 13.

FIG. 15A to FIG. 15D are explanatory diagrams of dose information mapsof a fluorescent agent (phosphor) in the dose control apparatus shown inFIG. 13.

FIG. 16 is a flow chart of a dose control program in the dose controlapparatus shown in FIG. 13.

FIG. 17 is an explanatory diagram of a fluorescence intensityimprovement attained by dose control in the dose control apparatus shownin FIG. 13.

FIG. 18 is a functional block diagram of a dose control apparatusaccording to a fourth embodiment of the present invention.

FIG. 19 is an explanatory diagram of the correction of dose informationmap of the fluorescent agent in the dose control apparatus shown in FIG.18.

FIG. 20 is a flow chart of a dose control program in the dose controlapparatus shown in FIG. 18.

FIG. 21 is a functional block diagram of a dose control apparatusaccording to a fifth embodiment of the present invention.

FIG. 22 is an explanatory diagram of a dose information table of afluorescent agent in the dose control apparatus shown in FIG. 21.

FIG. 23 is a flow chart of a dose control program in the dose controlapparatus shown in FIG. 21.

DETAIL DESCRIPTION OF THE PREFERRED EMBODIMENT

The embodiments of the present invention will be described below withreference to the drawings.

First Embodiment

FIG. 1 to FIG. 11 relate to a first embodiment of the present invention.FIG. 1 is an external view showing the appearance of a fluorescent agentconcentration measuring apparatus. FIG. 2 is a diagram showing a firstdisplay example of a display portion shown in FIG. 1. FIG. 3 is a blockdiagram showing the configuration of the fluorescent agent concentrationmeasuring apparatus shown in FIG. 1. FIG. 4 is a diagram showing lightabsorption and light emission characteristics of a sample in a testbottle shown in FIG. 2. FIG. 5 is a diagram showing a transmissioncharacteristic of a barrier filter shown in FIG. 2. FIG. 6 is a blockdiagram showing the configuration of a modification of the fluorescentagent concentration measuring apparatus shown in FIG. 1. FIG. 7 is adiagram showing a transmission characteristic of an excitation lightfilter shown in FIG. 6. FIG. 8 is a flow chart for explaining operationsof the fluorescent agent concentration measuring apparatus shown in FIG.2. FIG. 9 is a diagram showing an example of an analytical pattern groupstored in a pattern storage portion shown in FIG. 2 and composed of aplurality of analytical patterns reflecting the individual difference ona fluorescent agent basis. FIG. 10 is a diagram for explainingprocessing for comparing with each analytical pattern of the analyticalpattern group, shown in FIG. 8. FIG. 11 is a diagram showing a seconddisplay example of the display portion shown in FIG. 1.

As shown in FIG. 1, the fluorescent agent concentration measuringapparatus 1 of the present embodiment is portable and can be lent to apatient. The patient measures the concentration of the administeredfluorescent agent in the living body tissue with the apparatus byoneself at home or the like. Here, the fluorescent agent refers to adrug which emits fluorescence.

The fluorescent agent concentration measuring apparatus 1 has a loadingportion (container loading portion) 3, while a test bottle 2 containinga sample including saliva, urine, blood, or the like of the patient isloaded removably in the inside of the loading portion 3. A light shieldcover (light shield portion) 4 to block external light when the testbottle 2 is loaded in the inside is disposed on the upper surface ofthis loading portion 3.

A display portion 11 composed of, for example, LCD and the like, todisplay various data and an input switch portion 12 to input variousdata are disposed on the front surface of the fluorescent agentconcentration measuring apparatus 1. The input switch portion 12 iscomposed of, for example, a date setting switch 13 to designate a date,a patient ID setting switch 14 to designate the ID of the patient, afluorescent agent setting switch 15 to designate the fluorescent agentadministered to the patient, a start switch 16 to instruct the start ofmeasurement, and a keyboard portion 18 capable of inputting a characterstring, e.g., numbers or an alphabet, and the like. An output terminal20 to output signals of a peak time of the fluorescent agentconcentration and the like is disposed on a side surface or a back ofthe fluorescent agent concentration measuring apparatus 1.

As shown in FIG. 2, the data of date, the patient ID, the fluorescentagent name, and the like input by using the input switch portion 12, aswell as the number of inspections conducted by the patient by oneselfand the inspection results, are displayed on the display portion 11.

Specifically, as shown in FIG. 3, the fluorescent agent concentrationmeasuring apparatus 1 is configured to include a single-wavelength LED(single-wavelength laser light source) 21 serving as an excitation lightsource to radiate excitation light to the test bottle 2 loaded in theinside, a barrier filter (optical filter) 22 to transmit onlyfluorescence from the test bottle 2, a photoreceptor (fluorescencedetection portion) 23 to receive fluorescence through the barrier filter22 and output an electric signal, a detection processing circuit(fluorescence detection portion) 24 to conduct signal processing of theelectric signal from the photoreceptor 23 and detect the fluorescenceintensity, an operation circuit (fluorescent agent concentrationcalculation portion) 26 to compare the detection result from thedetection processing circuit 24 with an analytical pattern (describedbelow) stored in a pattern storage portion 25 serving as a curve datastorage portion and calculate the peak time of the concentration in atissue of the sample in the test bottle 2, and a control circuit 27 tocontrol these various circuits, the display portion 11, and the inputswitch portion 12.

As shown in FIG. 4, a predetermined wavelength of λ is positioned at aborder. The sample in the test bottle 2 absorbs excitation light with awavelength shorter than the wavelength of λ, and emits fluorescence witha wavelength longer than the wavelength of λ through excitation by theexcitation light.

Therefore, the excitation light with a single wavelength shorter thanthe wavelength of λ is radiated from the single-wavelength LED 21 to thesample in the test bottle 2, the light is received by the photoreceptor23 through the barrier filter 22 having a transmission characteristicshown in FIG. 5 and, thereby, only the fluorescence from the sample inthe test bottle 2 is detected by the photoreceptor 23.

Alternatively, as shown in FIG. 6, a white lamp (for example, a xenonlamp) 31 can be used as a white light source in place of thesingle-wavelength LED 21. In this configuration, only the light with awavelength shorter than the wavelength of λ may be radiated to the testbottle 2 by disposing an excitation light filter (transmission filter)32 having a transmission characteristic shown in FIG. 7 in between thewhite lamp 31 and the test bottle 2, and the fluorescence may bereceived by the photoreceptor 23 through the barrier filter 22.

The operations of the thus configured present embodiment will bedescribed.

When a fluorescent agent is administered into the living body of thepatient in a hospital or the like which the patient visits, the patientis lent the fluorescent agent concentration measuring apparatus 1 of thepresent embodiment from the hospital or the like, and disposes thisfluorescent agent concentration measuring apparatus 1 at home or thelike. At this time, the test bottle 2 and a predetermined reagent to bemixed to a sample, e.g., saliva, urine, or blood, are supplied togetherwith the fluorescent agent concentration measuring apparatus 1 from thehospital or the like to the patient.

The fluorescent agent concentration measuring apparatus 1 disposed athome or the like as described above is used. As shown in FIG. 8, at theinspection time of day previously instructed by the hospital or thelike, the patient takes a sample from saliva, urine, blood, or the likein step S1, and mix the sample and the supplied predetermined reagent soas to put into the test bottle 2 in step S2. In the case where thefluorescent agent in the sample is a fluorescent agent of PeT(Photo-induced Electron Transfer) system, this predetermined sample is adrug to activate the fluorescent agent in the sample.

In step S3, the test bottle containing the sample is loaded in theloading portion 3 of the fluorescent agent concentration measuringapparatus 1, the light shield cover 4 is closed and, thereby, the testbottle 2 is disposed in the inside of the fluorescent agentconcentration measuring apparatus 1 while being shielded from externallight.

Subsequently, the following processing is executed under the control ofthe control circuit 27. That is, in step S4, various data, e.g., thedata of date, the patient ID, and the fluorescent agent name, are inputby using the input switch portion 12 (the date setting switch 13, thepatient ID setting switch 14, the fluorescent agent setting switch 15,and the keyboard portion 18).

Although not shown in the drawing, for example, an RF-ID tag, in whichthe patient ID, the fluorescent agent name, and the like are recorded,may be disposed on the test bottle 2 and, in addition, an RF-IDcommunication device may be disposed in the fluorescent agentconcentration measuring apparatus 1, so that the patient ID and thefluorescent agent name recorded in the RF-ID tag may be taken into thefluorescent agent concentration measuring apparatus 1 by radio.

In step S5, the start switch 16 of the input switch portion is pusheddown and, thereby, an inspection of the fluorescent agent concentrationof the sample in the test bottle 2 is started.

When the inspection is started, the excitation light is radiated fromthe single-wavelength LED 21 to the test bottle 2. The fluorescenceemitted from the excited sample in the test bottle 2 is received by thephotoreceptor 23 through the barrier filter 22. The electric signal fromthe photoreceptor 23 is output to the detection processing circuit 24.

In step S6, the intensity of the fluorescence from the excited sample inthe test bottle 2 and the inspection time of day are compared with theanalytical pattern stored in the pattern storage portion 25 by theoperation circuit 26.

As shown in FIG. 9, since the concentrations of the fluorescent agentsin the living body are different on a type of the fluorescent agentbasis and, furthermore, the concentration varies due to the individualdifference even when the fluorescent agent is the same. Consequently, ananalytical pattern group composed of a plurality of analytical patternsreflecting the individual difference on a fluorescent agent basis isstored in the pattern storage portion 25, and the comparison with thesample is conducted by using a group of these analytical patterns. As anexample, FIG. 9 shows two groups of analytical patterns for afluorescent agent A (solid line) and a fluorescent agent B (brokenline), each group composed of three analytical patterns based on theindividual difference.

As described above, since the concentration of the fluorescent agent inthe living body varies depending on not only the type of fluorescentagent administered to the patient, but also the individual difference ofpatient, the times of day at which the concentrations of the fluorescentagents in the living body reach their peaks are different. In FIG. 9,peak points of the fluorescent agent A (solid line) are indicated byblack circles and peak points of the fluorescent agent B (broken line)are indicated by black triangles.

Therefore, in the comparison with the analytical pattern in step S6, theanalytical pattern group to be compared is selected based on the type offluorescent agent (fluorescent agent name) and, as shown in FIG. 10, theintensities of fluorescence (inspection results) from the sample andeach analytical pattern of the analytical pattern group at theinspection time of day are compared with each other.

The above-described comparison is conducted a plurality of times, e.g.,three times, and thereby, the peak time of day of the concentration ofthe fluorescent agent in the living body is estimated. Therefore, it isjudged whether or not the number of inspections has reached apredetermined number in step S7. When the number is not reached, in stepS8 as shown in FIG. 11, the time of day for the next inspection isdisplayed on the display portion 11 as the inspection result, and theprocessing is finished. When the number of inspections has reached apredetermined number and the peak time of day of the concentration ofthe fluorescent agent in the living body is estimated, as shown in FIG.2, the time of day for visit is displayed as the inspection result instep S9, and the processing is finished. The above-described peak timeestimation processing is conducted by a peak time estimation portionbuilt in the control circuit 27.

In step S9, the peak time of day of the concentration of the fluorescentagent in the living body may be output from the control circuit 27 tothe output terminal 20. The output terminal 20 is to be connected to,for example, an apparatus for administering the fluorescent agent intothe living body. In this manner, the apparatus for administering thefluorescent agent into the living body, for example, a dose controlapparatus 121 described below, can control the administration starttime, the dose, and the like of the fluorescent agent, based on the peakinformation attained through the output terminal 20.

Here, the estimation of the peak time of the concentration of thefluorescent agent in the living body will be described in detail. Theinspection times of day are different depending on the types offluorescent agent. The first inspection time of day is instructed fromthe hospital or the like, based on the administration of the fluorescentagent. The time of day for the following inspection is the time of day apredetermined time interval after the first inspection time.

When some fluorescent agent is administered, by conducting theinspection a plurality of times at a predetermined time interval, forexample, 3 times at a time interval of 6 hours, from the administrationtime of the fluorescent agent, it is made clear which analytical patternis applicable to the intensities of fluorescence (inspection results)from the sample at the plurality of inspection times of day by thecomparison. Consequently, the peak of the resulting applicableanalytical pattern is assumed as the peak time of day of theconcentration of this fluorescent agent in the living body.

For example, FIG. 10 is an example of 3 times at a time interval of 6hours from the administration time of day of the fluorescent agent,wherein it is estimated that the peak time of day of the concentrationof the fluorescent agent in the living body becomes the time of day 15hours elapsed from the last administration time of day.

As described above, in the present embodiment, since the fluorescentagent concentration measuring apparatus 1 is portable and can be lent toa patient, the patient is not required to stay in the hospital until theconcentration of the fluorescent agent in the living body tissue reachesits peak. As a result, the peak time of day of the concentration of thefluorescent agent in the living body tissue can be estimated only bymeasuring the fluorescent agent concentration in the sample of saliva,blood, or the like at home or the like at a predetermined time intervalwith the fluorescent agent concentration measuring apparatus 1.Therefore, it is possible to encourage the patient to visit the hospitalby notifying the patient of this peak time of day.

Second Embodiment

FIG. 12 is a block diagram showing the configuration of a fluorescentagent concentration measuring apparatus according to a second embodimentof the present invention.

Since the second embodiment is substantially the same as the firstembodiment, only the different points are described, and the sameconfigurations are indicated by the same reference numerals as those setforth above and explanations thereof will not be provided.

As shown in FIG. 12, in the configuration of the present embodiment, acommunication I/F 51 serving as a communication portion capable ofcommunicating with a wide-area network, e.g., Internet 50, is disposedin a fluorescent agent concentration measuring apparatus 1 and a patternstorage portion 25 is disposed in a hospital server 52 serving as anin-hospital external server connected to the Internet 50. Otherconfigurations and operations are equal to those in the firstembodiment.

The configuration of the present embodiment exhibits more outstandingportability since there is no need to dispose the pattern storageportion 25 in the inside of the fluorescent agent concentrationmeasuring apparatus 1. Since the information of the intensity offluorescence (inspection result) from the sample of the patient can beaccumulated in the hospital server 52, it becomes possible to generatevarious analytical patterns based on the information of the intensity offluorescence (inspection result) and store in the pattern storageportion 25 serving as a curve data storage portion. It is also possibleto omit the operation circuit 26 by allowing the hospital server 52 tohave an arithmetic function of the operation circuit 26.

In the fluorescence observation with a fluorescence endoscope or thelike through administration of a fluorescent drug by using thefluorescent agent concentration measuring apparatuses 1 explained in theabove-described first and second embodiments, the following embodimentscan be adopted as a dose control apparatus to maintain the fluorescentstate of the inspection object at a favorable state and anadministration system including the same.

Third Embodiment

FIG. 13 to FIG. 17 show a third embodiment of the present invention.FIG. 13 is an explanatory diagram of an entire system when afluorescence observation is conducted with an endoscope by using a dosecontrol apparatus. FIG. 14 is a functional block diagram of the dosecontrol apparatus. FIG. 15A to FIG. 15D are explanatory diagrams of doseinformation maps of a fluorescent agent. FIG. 16 is a flow chart of adose control program. FIG. 17 is an explanatory diagram of afluorescence intensity improvement attained by dose control.

In FIG. 13, reference numeral 101 denotes an inspection object, e.g., aliving body, to be subjected to a fluorescence observation by afluorescence endoscope system 102. This inspection object isadministered intravenously with a fluorescent drug (fluorescent agent,phosphor), e.g., a solution, in which an indocyanine green derivedlabeled antibody is dissolved, from a fluorescent agent administrationsystem 103.

Since the indocyanine green derived labeled antibody described here asan example has an affinity for a lesion, e.g., a cancer, as described inPCT/WO96/23525, it accumulates in the lesion as time passes after beingadministered into a body. Since the structure is similar to that ofindocyanine green (ICG) previously used for the inspection of the liverfunction, a high degree of safety is exhibited against the living body.

The fluorescence endoscope system 102 is primarily configured to includeat least a light source 104 to emit excitation light, an endoscope 105to introduce the excitation light into a living body lumen 101 a andobserve fluorescence emitted from the lesion site, a camera control unit107 to drive a color image pickup device 106 built in the endoscope 105so as to convert the fluorescence figure of the lesion to a videosignal, an image processor 108 to process the video signal so as tofacilitate discrimination between a lesion site and a normal portion,and a monitor 109 to display the output from the image processor 108 asan image.

The light source 104 incorporates a laser 110, e.g., excimer, He—Cd, orargon, to emit light in a blue or ultraviolet region.

The endoscope 105 is primarily configured to include a light guide 111to lead laser light emitted from the laser 110 to the living body lumen101 a, a concave lens 112 to diffuse the laser light for illumination,objective lenses 113 to throw a fluorescence figure of the lesion siteto the color image pickup device 106, and an optical filter 114 totransmit specific wavelengths of the fluorescence figure from theobjective lenses 113. Here, the optical filter 114 has a predeterminedtransmission characteristic.

Although not shown in the drawing, light source 104 includes a xenonlamp for emitting white light and a switching portion to switch betweenthe light from the laser and the light from the xenon lamp and supply tothe light guide 111. Furthermore, the endoscope 105 incorporates animage pickup device, although not shown in the drawing, to pick up afigure by the white light.

Consequently, in the fluorescence endoscope system 102 having theabove-described configuration, the laser light emitted from the laser110 is incident on the light guide 111 built in the endoscope 105, andis led to the living body lumen 101 a. The laser light is diffused bythe concave lens 112 and is radiated to the living body lumen 101 a.Fluorescence is emitted from a lesion site and a surrounding normalportion by this laser light, the resulting fluorescence passes objectivelenses 113, and is projected on the color image pickup device 106through the optical filter 114. The signal processing is conducted bythe camera control unit 107 and the image processor 108 so as to displayon the monitor 109, and fluorescence observation is conducted.

The fluorescence endoscope system 102 is not limited to that in thepresent third embodiment, and may have other configurations.

On the other hand, the fluorescent agent administration system 103 isprimarily configured to include a drip infusion container 119 hung by ahanger component 118 at the top portion of a column 117 of an infusionstand 116, an automatic administration apparatus 120 serving as anautomatic administration portion which is fixed to some midpoint of thecolumn 117 of the same infusion stand 116 and administers a fluorescentdrug (fluorescent agent, phosphor) supplied from the drip infusioncontainer 119 to an inspection object 101, a dose control apparatus 121to control the administration from the automatic administrationapparatus 120 to the inspection object 101, a living body informationdetection portion 200 to detect the living body function information ofthe inspection object 101, and a fluorescent agent concentrationmeasuring apparatus 1 to measure the concentration of the fluorescentagent in the living body.

An apparatus having a configuration and a function similar to those ofthe fluorescent agent concentration measuring apparatuses of theabove-described first and second embodiments is applied to thefluorescent agent concentration measuring apparatus 1.

The above-described fluorescent drug (phosphor), e.g., a solution, inwhich an indocyanine green derived labeled antibody is dissolved, isencapsulated in the drip infusion container 119. The drip infusioncontainer 119 is connected to the automatic administration apparatus 120through a drip infusion tube 122 and, thereby, the fluorescent drug(phosphor) is supplied into a syringe 123 of the automaticadministration apparatus 120.

The automatic administration apparatus 120 is, for example, an automaticdrip infusion apparatus, and allows the fluorescent agent (phosphor)from the drip infusion container 119 to drip in the syringe 123.Subsequently, the fluorescent agent (phosphor) is administered to thevein of the inspection object 101 from the syringe 123 through a dripinfusion tube 125. At this time, the intravenous administration of thefluorescent agent (phosphor) to the inspection object 101 at a desiredflow rate can be conducted automatically or manually by variablyadjusting the pushing force of a pushing component 124 disposed at theend portion of the syringe 123, based on the control signal from thedose control apparatus 121 or an operation by the operator.

The living body information detection portion 200 is to detect theliving body information, and is disposed on a skin of the inspectionobject 101 while being electrically connected to the dose controlapparatus 121. The living body information detection portion 200 detectsthe living body function information of the inspection object 101, andtransmits the living body function information to the dose controlapparatus 121. Here, the above-described living body functioninformation refers to the information, such as the heart rate, theoxygen saturation, and the blood pressure, which relate to the metabolicinformation and can be detected through the skin of the inspectionobject 101. In the measurement of the living body function information,known measurement devices can be used appropriately as the living bodyinformation detection portion 200. For example, a measurement device,e.g., a pulse oxymeter, is used for the measurement of the oxygensaturation.

For the dose control apparatus 121, an automatic administration starttime, the administration finishing condition, and the like are input bythe operator, the living body function information is input by theliving body information detection portion 200, and the dose incorrespondence to the administration time is set based on a doseinformation map while following the dose control program describedbelow. When the administration time is reached, the dose controlapparatus 121 outputs an output signal in correspondence to the dose tothe automatic administration apparatus 120 (in the case where automaticadministration is conducted by the automatic administration apparatus120) and, in addition, the dose, the administration time, and the likeare displayed on a monitor portion 121 g.

The dose control apparatus 121 corrects the dose or the administrationtiming of the fluorescent agent (phosphor) when the living body functioninformation of the inspection object 101 detected by the living bodyinformation detection portion 200 varies during the automaticadministration by the automatic administration apparatus 120.

In order to realize the above-described function, the dose controlapparatus 121 is primarily configured to include, for example, a timerportion 121 a, a dose data memory portion 121 b, a living bodyinformation reference value memory portion 121 c, a dose data correctionportion 121 d, an administration finishing condition judgment portion121 e, a main control portion 121 f, and the monitor portion 121 g, asshown in FIG. 14.

The timer portion 121 a is a so-called timer, and an elapsed time isread by the main control portion 121 f, as needed.

In the dose data memory portion 121 b, a required dose determinedbeforehand by an experiment, theoretical calculation, and the like isstored as a map in correspondence to the time (dose information map). Inthis dose information map, for example, the dose Ks is set in such a wayas to decrease continuously and linearly with the passage of time afterthe administration start time T1, as shown in FIG. 15A. The doseinformation map may have a nonlinear characteristic as shown in FIG.15B. This characteristic is essentially determined by an experiment,theoretical calculation, and the like. The dose information map storedin the dose data memory portion 121 b is read by the dose datacorrection portion 121 d, as needed.

The dose information map is not limited to the above-described form. Forexample, the dose may not be decreased continuously with the passage oftime, but a constant dose may be administered continuously or the dosemay be fluctuated continuously with the passage of time. The dose maynot be decreased with the passage of time as shown in FIG. 15A, but thedose may be set to increase continuously and linearly with the passageof time after the administration start time T1 as shown in FIG. 15C, forexample. Likewise, for FIG. 15B, the dose may not be decreased with thepassage of time, but the dose may be set to increase continuously withthe passage of time after the administration start time T1 while anonlinear characteristic is exhibited as shown in FIG. 15D, for example.

The general living body function information, e.g., a heart rate, on aweight, age, sex, and the like basis is stored as living bodyinformation reference values in the living body information referencevalue memory portion 121 c. These living body information referencevalues are read by the dose data correction portion 121 d, as needed.

When the automatic administration apparatus 120 is in operation, theliving body function information of the inspection object 101 is alwaysinput from the living body information detection portion 200 into thedose data correction portion 121 d. The dose data correction portion 121d compares the input living body function information with the livingbody function information reference value stored in the living bodyinformation reference value memory portion 121 c, and judges whether thedose and the administration time are appropriate or not. When it isjudged as being not appropriate, the dose data correction portion 121 dcorrects at least one of the dose and the administration time. Forexample, correction is conducted in such a way that the administrationtime is increased when the heart rate is increased, the administrationtime is decreased when the heart rate is decreased, and the like. Thecorrection signals of the dose and the administration time aretransmitted from the dose data correction portion 121 d to the automaticadministration apparatus 120. The automatic administration apparatus 120adjusts the administration of the fluorescent agent (phosphor), based onthe correction signals. A series of these processes is conducted apredetermined times within the time of administration of the fluorescentagent (phosphor).

The administration finishing condition judgment portion 121 e judgeswhether the administration finishing condition has been input by theoperator and whether this administration finishing condition has beensatisfied or not, and outputs a signal to the main control portion 121 fwhen the condition has been satisfied. Here, the administrationfinishing condition refers to, for example, a total time of automaticadministration of the fluorescent agent (phosphor), a total dose of thefluorescent agent (phosphor), intentional OFF of the automaticadministration (switching operation by the operator), and the like. Whenany one of these conditions has been satisfied, a signal for finishingthe administration is output to the main control portion 121 f.

The automatic administration start time T1 is input into the maincontrol portion 121 f by the operator. After the main control portion121 f judges that the automatic administration start time T1 is reached,the main control portion 121 f sets the dose of the fluorescent agent(phosphor) in correspondence to the time based on the dose informationmap of the dose data memory portion 121 b.

When the automatic administration apparatus 120 is in operation (whenthe automatic administration apparatus 120 is ON), the main controlportion 121 f outputs a signal in correspondence to the dose to theautomatic administration apparatus 120, and allows the monitor portion121 g to display the dose and the administration time. On the otherhand, when the automatic administration apparatus 120 is not inoperation (when the automatic administration apparatus 120 is OFF), themain control portion 121 f allows the monitor portion 121 g to displayan indication that the automatic administration apparatus 120 is OFF anddisplay the dose and the administration time. When a signal forfinishing the administration is input from the administration finishingcondition judgment portion 121 e, the automatic administration isallowed to finish.

In the case where the fluorescent agent (phosphor) is administered againinto the living body after the automatic administration is finished, themain control portion 121 f judges the start time of readministrationbased on the peak time of the concentration of the fluorescent agent(phosphor) in the living body, the peak time being input from thefluorescent agent concentration measuring apparatus 1. That is, the maincontrol portion 121 f sets the start time of readministration at apredetermined time before or after the peak time of the concentration ofthe fluorescent agent (phosphor) in the living body, the peak time beingestimated by the fluorescent agent concentration measuring apparatus 1.It is preferable that the start time of readministration is set based onthe time difference between the administration start time of the lastadministration and the estimated peak time of the concentration in theliving body, although not limited to this. When the main control portion121 f judges that the set start time of readministration is reached, themain control portion 121 f sets the dose of the fluorescent agent(phosphor) in correspondence to the time, as described above. In thismanner, the dose control apparatus 121 can control in such a way thatthe concentration of the fluorescent agent (phosphor) in the living bodyreaches again its peak a predetermined time after the peak time of theconcentration in the living body.

As described above, the dose control apparatus 121 is configured toinclude the functions of an administration start judgment portion, adose setting portion, and an output portion.

The dose control program executed by the dose control apparatus 121 willbe described below with reference to the flow chart shown in FIG. 16.

In step S101, the automatic administration start time T1 input by theoperator is read. Subsequently, step S102 is executed, wherein it isjudged whether the automatic administration start time T1 is reached ornot.

When it is judged in step S102 that the automatic administration starttime T1 is reached, step S103 is executed, wherein the dose is set basedon the time from the start of the automatic administration withreference to the predetermined map (dose information map).

Thereafter, step S104 is executed, wherein it is judged whether theautomatic administration apparatus 120 is ON or not. When the result ofthis judgment is ON, step S105 is executed, wherein the living bodyinformation detection portion 200 detects the living body functioninformation of the inspection object 101 and transmits the living bodyfunction information to the dose data correction portion 121 d.

Step S106 is executed, wherein the dose data correction portion 121 djudges whether the dose of the fluorescent agent (phosphor) isappropriate or not, based on the living body function information. Whenit is appropriate as a result, step S107 is executed, wherein the signalin correspondence to the dose set in step S103 is output to theautomatic administration apparatus 120, and step S110 is executed.Conversely, when it is not appropriate, step S108 is executed, whereinthe dose data correction portion 121 d corrects at least one of the doseand the administration time and outputs the signal in correspondence tothe corrected dose or administration time, and step S110 is executed.

On the other hand, when the automatic administration apparatus 120 isOFF in the above-described step S104, step 109 is executed, wherein themonitor portion 121 g is allowed to display that the automaticadministration apparatus is OFF, and step S110 is executed.

When step S110 is executed after step S107, step S108, or step S109, themonitor portion 121 g is allowed to display the dose and theadministration time. In the case where the dose and the administrationtime are displayed on the monitor portion 121 g during the automaticadministration apparatus 120 is OFF, the operator administers thefluorescent agent (phosphor) by oneself.

Step S111 is executed, wherein it is judged whether the administrationfinishing condition is established or not. When the administrationfinishing condition is not established, the processing from step S103 isrepeated. When the administration finishing condition is established,step S112 is executed. Each data (clocked time and the like) is cleared,and step S113 is executed. The monitor portion 121 g is allowed todisplay finish of the administration, and the program is finished.

That is, in the previously known case, as indicated by a broken lineshown in FIG. 17, a peak of fluorescence intensity is exhibited apredetermined time Tp after the initial administration, and after that,the fluorescence intensity is decreased gradually since the fluorescentagent (phosphor) is metabolized. However, in the case where thefluorescent agent (phosphor) is administered by using the dose controlapparatus 121 according to the present third embodiment, as indicated bya solid line shown in FIG. 17, the fluorescence intensity close to peakcan be maintained for a while after the peak is reached.

Consequently, even in the state in which the fluorescence intensityprecisely at the peak is not attained due to, for example, theindividual difference of the inspection object 101, a favorablefluorescence observation can be conducted nearly at the peak withflexibility.

Since the state in which the fluorescence intensity is close to the peakcan be maintained for a long time, there is no need to precisely graspthe time at which the fluorescence intensity reaches its peak, so thatleeway can be given to the observation and the observation can beconducted stably.

There is no need to conduct a plurality of times of observation aimingat the peak of the fluorescence intensity and, therefore, an observationcan be conducted while very small load is applied to the observer andthe inspection object 101.

When the automatic administration apparatus 120 is in operation, thedose data correction portion 121 d can correct repeatedly the dose andthe administration time of the fluorescent agent (phosphor), based onthe living body function information of the inspection object 101. As aresult, an optimum dose of fluorescent agent (phosphor) can beadministered from the automatic administration apparatus 120 to theinspection object 101 in correspondence to the variations in themetabolism of the inspection object 101 with time.

The dose control apparatus 121 can control in such a way that theconcentration of the fluorescent agent in the living body reaches againits peak after the readministration time, based on the peak time of theconcentration of the fluorescent agent (phosphor) in the living bodyestimated by the fluorescent agent concentration measuring apparatus 1.Here, the state in which the fluorescence intensity is close to the peakcan be maintained for a longer time by the readministration of thefluorescent agent at a predetermined time before the estimated peak timeof the concentration in the living body.

Fourth Embodiment

FIG. 18 to FIG. 20 show a fourth embodiment of the present invention.FIG. 18 is a functional block diagram of a dose control apparatus. FIG.19 is an explanatory diagram of the correction of dose information mapof the fluorescent agent (phosphor). FIG. 20 is a flow chart of a dosecontrol program. The present fourth embodiment is different from theabove-described third embodiment in the point that the dose informationmap in the dose control apparatus is freely corrected in correspondenceto the metabolic information, and other configuration and operation aresimilar to those in the third embodiment. Therefore, the sameconfigurations are indicated by the same reference numerals as those setforth above and explanations thereof will not be provided.

That is, as shown in FIG. 18, for a dose control apparatus 131, theautomatic administration start time, the administration finishingcondition, the metabolic information (described below), and the like areinput by an operator, the living body function information is input bythe living body information detection portion 200, and the dose and thelike in correspondence to the administration time is set based on a doseinformation map, which is set after correction based on the metabolicinformation, while following the dose control program described below.When the administration time is reached, the dose control apparatus 131outputs an output signal in correspondence to the dose to the automaticadministration apparatus 120 (in the case where automatic administrationis conducted by the automatic administration apparatus 120) and, inaddition, the dose, the administration time, and the like are displayedon the monitor portion 121 g.

The dose control apparatus 131 corrects the dose or the administrationtiming of the fluorescent agent (phosphor) when the living body functioninformation of the inspection object 101 detected by the living bodyinformation detection portion 200 varies during the automaticadministration by the automatic administration apparatus 120.

Here, the above-described metabolic information is attained beforehandfrom the inspection object 101 through, for example, an inspection ofthe concentration in the blood. For example, the information is attainedfrom the concentration of an enzyme, e.g., γ-GTP(γ-glutamyltranspeptidase) and GOT (glutamic-oxaloacetic transaminase),in the blood or an enzyme, e.g., cathepsin B, cathepsin L, or uPA(urokinase-type plasminogen activator), observed when a cancer occurs.

In order to realize the above-described dose control function, the dosecontrol apparatus 131 is primarily configured to include, for example, atimer portion 121 a, an administration finishing condition judgmentportion 121 e, a monitor portion 121 g, a dose data memory portion 131b, a living body information reference value memory portion 131 c, adose data correction portion 131 d, and a main control portion 131 f, asshown in FIG. 18.

In the dose data memory portion 131 b, a required dose, which isdetermined beforehand by an experiment, theoretical calculation, and thelike and is in correspondence to the above-described metabolicinformation reference value and living body function informationreference value, is stored as a map in correspondence to the time (doseinformation map). In this dose information map, for example, the dose Ksis set in such a way as to decrease continuously and linearly with thepassage of time after the administration start time T1, as indicated bya solid line shown in FIG. 19. The dose information map stored in thedose data memory portion 131 b is read by the dose data correctionportion 131 d, as needed.

The general metabolic information of the above-described enzyme and theliving body function information, e.g., a heart rate, on a weight, age,sex, and the like basis is stored as metabolic information referencevalues and living body function information reference values,respectively, in the living body information reference value memoryportion 131 c. These metabolic information reference values and livingbody function information reference values are read by the dose datacorrection portion 131 d, as needed.

The metabolic information of the inspection object 101 is input by theoperator into the dose data correction portion 131 d. The living bodyfunction information is input from the living body information detectionportion 200. The metabolic information reference values and the livingbody function information reference values are input from the livingbody information reference value memory portion 131 c. The doseinformation map is input from the dose data memory portion 131 b.

The dose data correction portion 131 d compares the metabolicinformation of the inspection object 101 with the metabolic informationreference value, and judges the magnitude correlation. For example, whenthe metabolic information of the inspection object 101 is larger thanthe metabolic information reference value by 10%, the administrationtime of the fluorescent agent (phosphor) is corrected so as to increaseby 10%. Conversely, when the metabolic information of the inspectionobject 101 is smaller than the metabolic information reference value by10%, the administration time of the fluorescent agent (phosphor) iscorrected so as to decrease by 10%. An example of this correction isindicated by broken lines shown in FIG. 19. The example of thecorrection shown here is no more than one example, and there may beother examples of the correction (for example, the proportion of thetime increased by the correction is differentiated from that of the timedecreased by the correction). The dose may be increased with the passageof time in contrast to that shown in FIG. 19, wherein the dose isdecreased, and the correction may be conducted by the dose datacorrection portion 131 d in such a way that the increasing rate ischanged. Furthermore, the above-described correction methods may becombined, so that the dose is changed and the finish time is changedcorrespondingly, or the correction may be conducted by the dose datacorrection portion 131 d in such a way that the increasing rate ischanged.

When the automatic administration apparatus 120 is in operation, theliving body function information of the inspection object 101 is alwaysinput from the living body information detection portion 200 into thedose data correction portion 131 d. The dose data correction portion 131d compares the input living body function information with the livingbody function information reference value stored in the living bodyinformation reference value memory portion 131 c, and judges whether thedose and the administration time are appropriate or not. When it isjudged as being not appropriate, the dose data correction portion 131 dcorrects at least one of the dose and the administration time. Forexample, correction is conducted in such a way that the administrationtime is increased when the heart rate is increased, the administrationtime is decreased when the heart rate is decreased, and the like. Thecorrection signals of the dose and the administration time aretransmitted from the dose data correction portion 131 d to the automaticadministration apparatus 120. The automatic administration apparatus 120adjusts the administration of the fluorescent agent (phosphor), based onthe correction signals. A series of these processes is conducted apredetermined times within the time of administration of the fluorescentagent (phosphor).

The automatic administration start time T1 is input into the maincontrol portion 131 f by the operator. After the main control portion131 f judges that the automatic administration start time T1 is reached,the main control portion 131 f sets the dose of the fluorescent agent(phosphor) in correspondence to the time based on the dose informationmap corrected by the dose data correction portion 131 d. When theautomatic administration apparatus 120 is in operation (when theautomatic administration apparatus 120 is ON), the main control portion131 f outputs a signal in correspondence to the dose to the automaticadministration apparatus 120, and allows the monitor portion 121 g todisplay the dose and the administration time. On the other hand, whenthe automatic administration apparatus 120 is not in operation (when theautomatic administration apparatus 120 is OFF), the main control portion131 f allows the monitor portion 121 g to display an indication that theautomatic administration apparatus 120 is OFF and display the dose andthe administration time. When a signal for finishing the administrationis input from the administration finishing condition judgment portion121 e, the automatic administration is allowed to finish.

In the case where the fluorescent agent (phosphor) is administered againinto the living body after the automatic administration is finished, asin the third embodiment, the main control portion 131 f judges the starttime of readministration, based on the peak time of the concentration ofthe fluorescent agent in the living body, the peak time being input fromthe fluorescent agent concentration measuring apparatus 1. When the maincontrol portion 131 f judges that the set start time of administrationis reached, the main control portion 131 f sets the dose of thefluorescent agent in correspondence to the time. In this manner, thedose control apparatus 131 can control in such a way that theconcentration of the fluorescent agent in the living body reaches againits peak a predetermined time after the peak time of the concentrationin the living body.

As described above, the dose control apparatus 131 is configured toinclude the functions of an administration start judgment portion, adose setting portion, and an output portion.

The dose control program executed by the dose control apparatus 131 willbe described below with reference to the flow chart shown in FIG. 20. Instep S201, the automatic administration start time T1 input by theoperator is read. Subsequently, step S202 is executed, wherein it isjudged whether the automatic administration start time T1 is reached ornot.

When it is judged that the automatic administration start time T1 isreached in step S202, step S203 is executed, wherein the metabolicinformation is read.

Step S204 is executed, wherein the metabolic information reference valueis read from the data base (the dose data memory portion 131 b).

Step S205 is executed. The metabolic information read in step S203 iscompared with the metabolic information reference value read in stepS204, and the correction value of the administration time, that is, thedegree of increase by the correction or the degree of decrease by thecorrection, is arithmetically calculated.

Step S206 is executed, wherein the predetermined map (dose informationmap) is corrected based on the correction value arithmeticallycalculated in step S205.

Step S207 is executed, wherein the dose is set based on the time fromthe start of the automatic administration with reference to the doseinformation map corrected in step S206.

Thereafter, step S208 is executed, wherein it is judged whether theautomatic administration apparatus 120 is ON or not. When the result ofthis judgment is ON, step S209 is executed, wherein the living bodyinformation detection portion 200 detects the living body functioninformation of the inspection object 101 and transmits the living bodyfunction information to the dose data correction portion 131 d.

Step S210 is executed, wherein the dose data correction portion 131 djudges whether the dose of the fluorescent agent (phosphor) isappropriate or not based on the living body function information. Whenit is appropriate as a result, step S211 is executed, wherein the signalin correspondence to the dose set in step S207 is output to theautomatic administration apparatus 120, and step S214 is executed.Conversely, when it is not appropriate, step S212 is executed, whereinthe dose data correction portion 131 d corrects at least one of the doseand the administration time and output the signal in correspondence tothe corrected dose or administration time, and step S214 is executed.

On the other hand, when the automatic administration apparatus 120 isOFF in the above-described step S208, step 213 is executed, wherein themonitor portion 121 g is allowed to display that the automaticadministration apparatus is OFF, and step S214 is executed.

When step S214 is executed after step S211, step S212, or step S213, themonitor portion 121 g is allowed to display the dose and theadministration time. In the case where the dose and the administrationtime are displayed on the monitor portion 121 g during the automaticadministration apparatus 120 is OFF, the operator administers thefluorescent agent (phosphor) by oneself.

Step S215 is executed, wherein it is judged whether the administrationfinishing condition is established or not. When the administrationfinishing condition is not established, the processing from step S207 isrepeated. When the administration finishing condition is established,step S216 is executed. Each data (clocked time and the like) is cleared,and step S217 is executed. The monitor portion 121 g is allowed todisplay finish of the administration, and the program is finished.

As described above, according to the present fourth embodiment, theeffects described for the above-described third embodiment can beexerted, as a matter of course. Furthermore, since the dose informationmap is set after being corrected based on the metabolic information, thepeak of the fluorescence intensity can be stably and preciselymaintained for a long time without being influenced by the individualdifference of the inspection object 101 and the variations with time ofthe metabolism, so that the fluorescence observation can easily beconducted.

Fifth Embodiment

FIG. 21 to FIG. 23 show a fifth embodiment of the present invention.FIG. 21 is a functional block diagram of a dose control apparatus. FIG.22 is an explanatory diagram of a dose information table of afluorescent agent (phosphor). FIG. 23 is a flow chart of a dose controlprogram. The present fifth embodiment is different from theabove-described first embodiment in the point that the administration ofa fluorescent agent (phosphor) by the dose control apparatus isconducted at a predetermined time interval, and other configuration andoperation are similar to those in the above-described first embodiment.Therefore, the same configurations are indicated by the same referencenumerals as those set forth above and explanations thereof will not beprovided.

That is, in FIG. 21, reference numeral 141 denotes a dose controlapparatus according to the present fifth embodiment, and an automaticadministration start time, an administration finishing condition, andthe like are input into this dose control apparatus 141 by the operator.The dose control apparatus 141 sets the dose and the like on apredetermined time interval basis (on the number of administrationbasis) based on the dose information table, (in the case where automaticadministration is conducted by the automatic administration apparatus120) outputs an output signal in correspondence to the dose to theautomatic administration apparatus 120 when the administration isconducted and, in addition, display the dose, the administration time,and the like on the monitor portion 121 g, while following the dosecontrol program.

In order to realize the above-described dose control function, the dosecontrol apparatus 141 is primarily configured to include, for example, atimer portion 121 a, an administration finishing condition judgmentportion 121 e, a monitor portion 121 g, a dose data memory portion 141a, and a main control portion 141 b, as shown in FIG. 21.

In the dose data memory portion 141 a, a required dose, which isdetermined beforehand by an experiment, theoretical calculation, and thelike is stored as a table (dose information table) on a time intervalbasis (on the number of administration basis). In this dose informationtable, for example, the dose is set in such a way as to decrease with anincrease in the number of administration after the administration starttime T1, as shown in FIG. 22. The dose information table stored in thedose data memory portion 141 a is read by the main control portion 141b, as needed.

The automatic administration start time T1 is input into the maincontrol portion 141 b by the operator. After the main control portion141 b judges that the automatic administration start time T1 is reached,the main control portion 141 b sets the dose of the fluorescent agent(phosphor) on a predetermined time interval basis (on the number ofadministration basis) based on the dose information table stored in thedose data memory portion 141 a. When the automatic administrationapparatus 120 is in operation (when the automatic administrationapparatus 120 is ON), the main control portion 141 b outputs a signal incorrespondence to the dose to the automatic administration apparatus120, and allows the monitor portion 121 g to display the dose and theadministration time. On the other hand, when the automaticadministration apparatus 120 is not in operation (when the automaticadministration apparatus 120 is OFF), the main control portion 141 ballows the monitor portion 121 g to display an indication that theautomatic administration apparatus 120 is OFF and display the dose andthe administration time. When a signal for finishing the administrationis input from the administration finishing condition judgment portion121 e, the automatic administration is allowed to finish.

In the case where the fluorescent agent (phosphor) is administered againinto the living body after the automatic administration is finished, asin the third embodiment, the main control portion 141 b judges the starttime of readministration, based on the peak time of the concentration ofthe fluorescent agent in the living body, the peak time being input fromthe fluorescent agent concentration measuring apparatus 1. When the maincontrol portion 141 b judges that the set start time of administrationis reached, the main control portion 141 b sets the dose of thefluorescent agent in correspondence to the time. In this manner, thedose control apparatus 141 can control in such a way that theconcentration of the fluorescent agent in the living body reaches againits peak a predetermined time after the peak time of the concentrationin the living body.

As described above, the dose control apparatus 141 is configured toinclude the functions of an administration start judgment portion, adose setting portion, and an output portion. A dose information table,in which the dose is increased or fluctuated on a time interval basis incontrast to that shown in FIG. 22 where the dose is decreased, may bestored in the dose data memory portion 141 a and the table may be readby the main control portion 141 b.

The dose control program executed by the dose control apparatus 141 willbe described below with reference to the flow chart shown in FIG. 23. Instep S301, the automatic administration start time T1 input by theoperator is read. Subsequently, step S302 is executed, wherein it isjudged whether the automatic administration start time T1 is reached ornot.

When it is judged in step S302 that the automatic administration starttime T1 is reached, step S303 is executed, wherein the dose is set basedon a value of a counter CT of the number of automatic administrationwith reference to the predetermined table (dose information table). Thecounter CT of the number of automatic administration is a counter tocount the number of administration, and an initial value is set at 0.

Subsequently, step S304 is executed, wherein it is judged whether thecounter CT of the number of automatic administration is 0 (initial time)or not. When the counter CT of the number of automatic administration is0 (initial time), step S306 is executed successively to conduct theadministration of the fluorescent agent (phosphor).

When the counter CT of the number of automatic administration is not 0(initial time), step S305 is executed. It is judged whether the set timeTc has elapsed after the last administration. When the set time Tc haselapsed, step S306 is executed to conduct the administration of thefluorescent agent (phosphor).

When step S306 is executed to conduct the administration of thefluorescent agent (phosphor), it is judged whether the automaticadministration apparatus 120 is ON or not. In the case of ON, step S307is executed, wherein a signal in correspondence to the dose set in stepS303 is output to the automatic administration apparatus 120.Subsequently, step S308 is executed, wherein the counter CT of thenumber of automatic administration is incremented (CT=CT+1) for the nextadministration, and step S310 is executed.

Conversely, when the automatic administration apparatus 120 is OFF, step309 is executed, wherein the monitor portion 121 g is allowed to displaythat the automatic administration apparatus is OFF, and step S310 isexecuted.

When step S310 is executed after step S308 or step S309, the monitorportion 121 g is allowed to display the dose and the administrationtime. In the case where the dose and the administration time aredisplayed on the monitor portion 121 g during the automaticadministration apparatus 120 is OFF, the operator administers thefluorescent agent (phosphor) by oneself.

Step S311 is executed, wherein it is judged whether the administrationfinishing condition is established or not. When the administrationfinishing condition is not established, the processing from step S303 isrepeated. When the administration finishing condition is established,step S312 is executed. Each data (clocked time, the counter CT of thenumber of automatic administration, and the like) is cleared, and stepS313 is executed. The monitor portion 121 g is allowed to display finishof the administration, and the program is finished.

As described above, the effects as in the above-described thirdembodiment can be exerted by administering the fluorescent agent(phosphor) at a predetermined time interval as in the fifth embodiment.

In the above-described third to fifth embodiments, the fluorescent drug(fluorescent agent, phosphor) is administered intravenously, althoughnot limited to this. The administration may be conducted to theinspection object 101 orally or by spraying in the body. For the oraladministration, the monitor portion 121 g displays the administrationtiming for the oral administration of the fluorescent agent. Theinspection object 101 takes a predetermined dose of fluorescent drugaccording to the displayed administration timing. For the spraying inthe body, a drip infusion tube 125 is inserted into an endotherapyproduct insertion channel (not shown in the drawing) disposed in theinside of the endoscope 105 of the fluorescence endoscope system 102serving as an internal medical device. According to this configuration,the fluorescent agent dripped from the drip infusion container 119 ofthe automatic administration apparatus 120 is sprayed into the livingbody lumen 101 a of the inspection object 101 from the vicinity of thedistal end of the endoscope 105 through the drip infusion tube 125.

In the explanation of each of the above-described embodiments, thefluorescent agent (phosphor), e.g., a solution, in which an indocyaninegreen derived labeled antibody is dissolved, is taken as an example.However, it is a matter of course that the present invention can beapplied to other fluorescent agents.

The present invention is not limited to the above-described embodiments,and various modifications and rearrangements can be made within thescope of the gist of the present invention.

1. A fluorescent agent concentration measuring method comprising: afluorescence detection step of detecting fluorescence from a samplecontaining a body fluid taken from a living body administered with afluorescent drug; a fluorescent agent concentration calculation step ofcalculating the concentration of the drug in the living body, based on adetection signal from the fluorescence detection step; and a peak timeestimation step of estimating the peak time after administration of thedrug into the living body, when the concentration of the drug in theliving body tissue is the highest, based on the elapsed time afteradministration of the drug to the living body and the calculatedconcentration of the drug.
 2. A dose control method comprising: afluorescence detection step of detecting fluorescence from a samplecontaining a body fluid taken from a living body administered with afluorescent drug; a fluorescent agent concentration calculation step ofcalculating the concentration of the drug in the living body, based on adetection signal from the fluorescence detection step; a peak timeestimation step of estimating the time after administration of the druginto the living body, when the concentration of the drug in the livingbody tissue is the highest, based on the elapsed time afteradministration of the drug to the living body and the calculatedconcentration of the drug; an administration start judgment step ofjudging whether a predetermined time has elapsed or not and judging thestart of administration of the drug when the predetermined time haselapsed; a dose setting step of setting at least one of the dose and theadministration time of the drug, based on the predetermined doseinformation of the drug after the judgment of the start ofadministration in the administration start judgment step; and an outputstep of performing at least one of functions of allowing the dose to bedisplayed and allowing the drug to be administered automatically, basedon the dose of the drug set in the dose setting step.